Comprehensive Guide to the Best Anti-Aging Supplements

Posted
on February 08, 2018

Anti-Aging, a
Multifaceted Approach:

When it comes to aging, the approach seems to be fairly one
sided: we want to increase our lifespans. While increasing lifespan may be possible, the idea of infinitely extending it seems somewhat
far-fetched. However, what does not seem far fetched is the idea of
facilitating a healthy aging process, rather than trying to completely halt it. The reality is that we will more than likely
never be able to fully halt aging, so why don’t we focus our efforts on aging in
a sustainable manner?

Think of it like wine, there is no realistic way to fully
halt the aging of wine. However, the aging process can be steered in a manner
that makes the wine develop properly over time to produce new and unique
flavours and textures. So much so that properly aged and extremely old wines
sell for enormous amounts of money such as a 1941 bottle of Inglenook Cabernet
Sauvignon from the Napa Valley which sold for a whopping $24,675 USD in 2004!
That being said, if the wine is aged improperly it will simply turn into
vinegar. This concept is of course only loosely related to human aging but there
are still a lot of parallels that exist between the two. For example, people who play high
impact sports throughout their lives have much higher incidences of knee problems
later in life despite possibly living very long lives. The same goes for wine. If you excessively knock wine around, it will likely not age as elegantly as
a bottle that is perfectly preserved without any major agitation. Individuals
who experience large amounts of neuro-oxidative damage in specific brain areas
can develop diseases that impair cognitive function despite being able to live
very long lives. Again, the same goes for wine. If a lot of oxygen is getting
into your wine while it is aging, it is very likely that the wine will loose
much of its flavor and color.

Based on the above, it is in our best interest to take
preventative steps during the aging process to ensure healthy aging so that we
not only live long lives but that we live long and happy lives. Below you will find a comprehensive guide that we have put together that goes over many of aspects of aging that
can be attenuated with a smart natural nootropic supplement regimen in order to potentially stop some of the
damaging aspects of aging.

What Causes Oxidative Stress?

One of the most common causes of age related decline is
from increased amounts of oxidative stress. One of the reasons why this
occurs is because, as we age, production of antioxidant enzymes such as
glutathione starts to decline, whereas the production of reactive oxygen species
start to increase. This is especially problematic if it starts to affect the
energy production center of cells, the mitochondria, which are particularly
sensitive to oxidative damage. If mitochondrion become damaged, then that has a
large downstream impact on many biological functions; especially within the
brain. Based on this knowledge, it is no surprise that red wine and resveratrol
has picked up a lot of traction in anti-aging and longevity circles. This is because resveratrol on paper is an excellent and comprehensive antioxidant.
Unfortunately, the bioavailability of resveratrol is lackluster, so to target
oxidation we would recommend the following highly efficacious antioxidant supplements:

N-Acetyl
L-Cysteine:
Benefits of N-acetyl L-cysteine include its ability to potentially increase the levels of glutathione, one of the most powerful antioxidant enzymes in our
body. N-acetyl L-cysteine may also scavenge hydroxyl radicals and
hypochlorous acid, two powerful oxidants produced in our bodies. Unfortunately,
N-acetyl L-cysteine does not protect against superoxide nor hydrogen peroxide-induced oxidation, thus it gets close to being the end all be all antioxidant supplement but it will need a little help to offer the most comprehensive protection
against oxidative stress.

Polygala
tenuifolia:
Benefits of polygala tenuifolia are very extensive (we will come back
to it later in this article) but most important to note in this section is that the benefits
of polygala tenuifolia include its potential ability to increase superoxide dismutase,
catalase and glutathione peroxidase. The most important of these being polygala tenuifolia’s ability to potentially increase superoxide dismutase - an enzyme that
breaks down superoxide to either hydrogen peroxide or free oxygen. Hydrogen peroxide is also an oxidant but to a
lesser extent than superoxide. Polygala tenuifolia also increases
levels of catalase which is an antioxidant enzyme that breaks down hydrogen peroxide
to water and hydroxyl radicals. The hydroxyl radicals also produce oxidative
damage, however, N-acetyl L-cysteine scavenges hydroxyl radicals preventing the
oxidative damage it can potentially induce.

The combination of N-aceyl L-cysteine and polygala tenuifolia may protect from the bulk of oxidative damage and has a very comprehensive
antioxidant effect.

What is Mitochondrial Function and How Can We Improve it?

Once we have oxidation under control, we can now focus on
improving mitochondrial function rather than preserving it. It has been found
that the more active and healthy our mitochondrion are, the better we age. One
major regulator of mitochondrial function and cellular energy is creatine. Surprisingly, creatine supplementation is often overlooked even though it
appears to have very potent anti-aging effects.

What Does Creatine Do?

A
creatine monohydrate supplement has the ability to support healthy
mitochondrial function whilst also preserving muscle mass and strength.
Creatine also has the potential to increase overall vitality due to increasing both
mitochondrial function and muscle function and thus it is very beneficial to
take a creatine monohydrate supplement in order to slow age-related
degeneration.

Mitochondrion

Another great mitochondrial function enhancer is a shilajit extract called Primavie. This is especially true when it is combined with ubiquinol, the reduced form of coQ10. Shilajit extract contains compounds such as fulvic acid and
dibenzo-alpha pyrones that are targeted mitochondrial antioxidants which also
increase ATP production. Shilajit is good for enhancing the effects of
ubiquinol, and ubiquinol reverses aging by itself, thus the combination significantly
helps in reducing the negative effects of aging. We could go into a lot more
depth about shilajit since it is a very interesting natural extract, but we
already did that in this blog post so we will spare you the details here!

Inflammation and the
Cholinergic System

Another major troublemaker when it comes to aging is
inflammation, both in our bodies and in our brains. As we age, we progressively
lose our ability to fight off inflammation which can lead to pain, mobility
issues, and perhaps most debilitating: cognitive decline. Because of this, it is no
surprise that turmeric and its beneficial compound curcumin are picking up a
lot of traction when it comes to the topic of aging. This is because turmeric
and curcumin do a fantastic job at supporting healthy inflammation levels throughout the body,
especially formulations such as Longvida curcumin which is designed to
specifically regulate inflammation in the brain.

One major pathway by which you may amplify and
improve upon the inflammation-regulating effects of turmeric and curcumin is to increase cholinergic signaling. More specifically, increase
cholinergic signaling in areas of the brain that have a high density of a
particular acetylcholine receptor called the alpha 7 nicotinic acetylcholine
receptor (α7nACh). The α7nACh receptor is a major regulator in the brains
inflammatory response that works by inhibiting the release of TNF-alpha, a major
inflammatory cytokine. To target this aspect of inflammation we have to inhibit
the tetrameric form of the acetyl choline esterase enzyme (AChE) an enzyme
which breaks down acetylcholine and is expressed only in the brain and
specifically in regions of the brain that have a high density of α7nACh
receptors such as the cerebral cortex, hippocampus and the amygdala. To inhibit tetrameric AChE, huperzine a may be used which appears to be a highly selective tetrameric AChE inhibitor. Huperzine a, by inhibiting tetrameric AChE leads to
increased levels of acetylcholine which then leads to activation of the α7nACh
receptors which, in turn, potently regulates inflammation in key areas of the brain prone
to inflammatory damage.

Another popular supplement for regulating inflammatory damage are fish oil supplements. Fish oil's beneficial effects include not
only regulating inflammation but also the maintenance of brain membranes. However,
just like curcumin and turmeric, this is already fairly well known so we decided
to find a synergistic and potentially improved addition and/or alternative to
fish oil supplements. Our top candidate for this is palmitoylethanolamide, which
may not only regulate inflammation and pain but also appears to be
highly neuroprotective. In fact, you can read more about that in this comprehensive blog we wrote about palmitoylethanolamide. A potentially-effective combination of ingredients to regulate both inflammation throughout the
body and the brain would be palmitoylethanolamide and huperzine a.

Additionally, a fish oil supplement may also be added to this combination and will be
especially beneficial if it is paired with a phosphatidylserine complex called
‘Smart PS’. Phosphatidylserine benefits brain health by both increasing cell
membrane synthesis, making it highly synergistic with fish oil. It also
downregulates acetylcholine esterase and thus it should also work
synergistically with huperzine a to regulate inflammation.

Cleaning Up the Brain

The brain is metabolically active which causes
the production of a lot of waste products that need to be adequately dealt
with. One of the ways our brains deals with containing, neutralizing and
eliminating damaging metabolic waste, is by sleeping. However, sleep tends to
become worse and worse as we age and one reason for this could be decreased
melatonin production. This is a quick and easy fix, simply take 300mcg of a melatonin supplement once per night which may improve overall sleep quality in addition to providing significant
antioxidant effects in the brain.

Sleep Stages

To be more specific, it appears
that our brain clears the most metabolic waste during slow wave sleep (SWS),
thus by increasing slow wave sleep we could potentially clear more metabolic waste products
from the brain during sleep which should lead to more restorative processes
taking place in the brain as we sleep. It has been found that rosmarinic acid,
which is found in both of our lemon balm extracts, speeds up the time it takes
to fall asleep and once asleep, enhances slow wave sleep. Theoretically this could
mean that lemon balm extract leads to more restorative sleep and, in conjunction with a
melatonin supplement, could make sleep come on more readily. A clinically-trialed lemon
balm extract called Cyracos has a very high amount of rosmarinic acid. This would
likely be the best lemon balm extract for promoting slow wave sleep.

One of the results of accumulated metabolic waste is a
pigment called lipofuscin. The older we get, the more build up of lipofuscin we
run into which is problematic since lipofuscin over time leads to cellular
degeneration. One way to potentially inhibit the formation of lipofuscin is to supplement with highly efficacious antioxidants, such as the
combination of N-acetyl L-cysteine and polygala tenuifolia, as lipofuscin is in
part produced during oxidative stress. Secondly, a supplement such as DMAE L-bitartrate (also known as Deanol - a DMAE L-bitartrate skin care
formulation) may be used to clear lipofuscin from the brain.

Regulating Nitric
Oxide with Agmatine Sulfate

Nitric oxide is a gaseous neurotransmitter, that is an
important regulator of blood flow and brain health. Nitric oxide is produced by
three different synthase enzymes, neuronal nitric oxide synthase (nNOS), inducible
nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Out
of all three, over activation of both nNOS and iNOS can produce neuronal damage
and as we age, our body becomes less efficient at regulating nitric oxide synthases
which leads to both inflammatory and oxidative damage. The only synthase that
can be beneficial when it is more active is eNOS, which prevents some of the
damage produced by iNOS and nNOS by producing vasodilation. As we age it
appears that specifically the activity of iNOS and nNOS gets upregulated which
could be caused by decreasing levels of agmatine. Agmatine, inhibits both iNOS and nNOS whilst
preserving eNOS activity and it is interesting to note that agmatine (an
endogenous neurotransmitter), levels decline significantly as we age. Based on
this, the best way to regulate NOS function as we age, is likely by using an agmatine
supplement to replenish declining agmatine levels. Agmatine effects are not
just limited to preventing excess nitric oxide levels, as it has been shown
that an agmatine supplement can help preserve and optimize memory as we age.

Polygala tenuifolia and Healthy Aging

As was mentioned earlier, we would be coming back to
polygala tenuifolia as it appears to be very useful at promoting healthy aging.
As we age, our brains slowly start to decrease in size and this is likely due
to the fact that neuroplasticity slows down. Decreased neuroplasticity can
decrease the resilience of our brains, negatively impact mood and can even
worsen memory. This is where polygala tenuifolia comes in again as one of the
main benefits of polygala tenuifolia is increased neuroplasticity. In addition
to that, it may also increase cholinergic function which is highly important in
maintaining and enhancing cognitive function. As we age, the levels of two
major neurotransmitters called dopamine and serotonin start to decline. Polygala
tenuifolia may help to increase the levels of these neurotransmitters. It is
unsurprising that in traditional Chinese medicine polygala tenuifolia is
highly regarded for its ability to improve cognitive function as we age as it
has many mechanisms by which it can do this.

What are Telomeres
and Why Are They Important?

Finally, the last part of the equation: telomeres. This is
where we really start to get into the actual idea of life extension, so we
thought it was appropriate to end things here and keep it brief, since our aim
is more focused on improving the aging process rather than extending life span.
That being said, there does seem to be some solid evidence behind telomere
lengthening leading to extended lifespan. Telomere length testing has become
widely available at reasonable costs recently, so a lot of people are focusing their
efforts on optimizing their telomere length as they now have access to a
concrete way of testing how their telomere length is changing. Often forgotten
about, an L-carnosine supplement may have significant anti-aging effects via
modulating telomeres. Carnosine benefits telomeres in two ways. Carnosine both
protects telomeres from potential damage while also promoting the lengthening
of telomeres. Due to this, carnosine is good for supplementation as a potential
life extender. In addition to the ability of an L-carnosine supplement to
increase life span, carnosine benefits skin health too which is also an
important aspect of aging.